DNA strand-breaking activity and mutagenicity of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), a Maillard reaction product of glucose and glycine.
Aqueous solution of glucose and glycine was heated under reflux for 4 h and extracted with ethyl acetate. Reversed phase HPLC of the extract revealed a new DNA strand-breaking substance, which was purified by repeated HPLC and identified as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP). DDMP induced DNA strand breaking in a dose- and time-dependent manner. It was active to break DNA strands at pH 7.4 and 9.4. Its pyranone skeleton was destroyed at the pH values. DNA strand breaking by DDMP was inhibited by superoxide dismutase, catalase, scavengers for hydroxyl radical, spin trapping agents and metal chelators, and the breaking was enhanced by Fe(III) ion. A mixture of DDMP and a spin trap DMPO gave electron spin resonance signals of a spin adduct DMPO-OH, indicating generation of hydroxyl radical. DDMP was found to be mutagenic to Salmonella typhimurium TA100 without metabolic activation. These results show DDMP generated active oxygen species to cause DNA strand breaking and mutagenesis.
Hiramoto
K
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Nasuhara
A
A
Michikoshi
K
K
Kato
T
T
Kikugawa
K
K
D002374:Catalase / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D007501:Iron / Q000494:pharmacology; D015416:Maillard Reaction; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D011714:Pyrans / Q000737:chemistry / Q000633:toxicity*; D011753:Pyrones; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology
C110646:2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one; D002614:Chelating Agents; D016166:Free Radical Scavengers; D009153:Mutagens; D011714:Pyrans; D011753:Pyrones; D013113:Spin Labels; D004247:DNA; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose; D005998:Glycine